Experimental Immune Complex Disease of the Lung

Abstract

There are increasing clinical (1-6), functional (7), radiological (4,5,6,8), and histological (3,(9)(10)(11)(12)(13)(14) evidences that interstitial pneumonitis with or without pulmonary fibrosis may develop in patients with underlying diseases which appear to be associated with circulating antigen-antibody complexes. The pathogenesis of these human lesions, however, has not been studied in experimental animal models. Rabbits with acute or chronic serum sickness have not shown pulmonary changes (15, 16). On the other hand, acute anaphylactic shock, a condition characterized by preferential precipitation of circulating antigen-antibody complexes within the lumina of pulmonary capillaries (17)(18)(19), is caused by a mechanism which has no relationship with chronic pulmonary diseases in man.These considerations have suggested the possibility that antigen-antibody complexes present in large amount and for prolonged periods of time in the circulation of rabbits may localize in their lungs, thereby producing inflammatory reactions comparable to those commonly seen in the kidneys of the same animals.The results of the studies described here show that rabbits making a hyperactive antibody response to injections of bovine serum albumin (BSA), 1 when maintained in a state of relative antigen-antibody equivalence by high, multiple, daily doses of BSA, develop membranous and/or proliferative lesions of the lung which are associated with deposition of antigen, host immunoglobulin, complement, and fibrinogen in pulmonary structures. The inflammatory changes, which are presumably produced by antigen-antibody complexes, cover the morphologic spectrum of certain human interstitial pneumonitis (20, 21). Materials and MethodsInduction of Serum Sickness.--58 female albino rabbits weighing 2-3 kg were purchased from a local breeder, and fed Purina rabbit pellets and water ad libitum. 51 rabbits were used

Latent pulmonary function abnormalities in children with Crohn's disease

“…There is increasing evidence that an immune system common to all mucosal surfaces exists, in which lymphocytes sensitized to antigens at one mucosal site may circulate and preferentially localize in the same or a different mucosal site. Indeed, experimental evidence for pulmonary damage by circulating immune complexes (CIC) in the pulmonary circulation has been provided [23]. Only one child in our population of patients, however, exhibited an elevated CIC level (unpublished data).…”

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

“…In monkeys and rabbits, rapid infusion rates lead to IC formation in antigen excess while slow infusion rates lead to IC formation in antibody excess (Brentjens et al 1974;. In monkeys, rapid infusion rates of BGG are associated with more severe infusion reactions with C3 decreases, C3a increases, leukopenia, respiratory distress, hypotension, and inflamed/hemorrhagic mesenteric vessels in the omentum Mahan et al 1993).…”

“…Studies of repeated-dose BSA infusion in sensitized rabbits indicate that acute anaphylactoid reactions occur that are mediated by BSA-IgG ICs, typical of generalized/systemic type 3 HSRs, and appear clinically and histologically similar to the acute infusion reactions in repeated BGG dose studies in monkeys (Brentjens et al 1974;Hebert et al 1991;Mahan et al 1993). In the BSA-sensitized, repeated-dose rabbit model, higher doses or more rapid infusion of antigen-elicited anaphylactoid reactions while slower injection rates (50-100 mg/day divided into two doses administered over a 2-to 8-hr period) allowed antigen persistence in the circulation even in rabbits with high anti-BSA antibody responses (Brentjens et al 1974).…”

Disorganizing-fibrosing processes in alveolar walls of interstitial pneumonia, "alveolopneumonitis": A morphopathological study.

“…The processes have been interpreted to be induced by localization and fixation of immune complexes in the alveolar walls through the phagocytic activity of cellular components in this structure which was revealed by electron microscopy. Later, Brentjens et al (1974) induced membranous and/or proliferative pneumontits, similar in certain features to human interstitial pneumonia, by means of daily injections of BSA into rabbits. The pulmonary lesions were associated with granular deposition in alveolar capillary walls and interstitium of antigen, host globulin, and complement, presumably of immune complexes.…”